The primary goal of this project is to evaluate, through phase II randomized clinical trials for brain, head and neck, lung and liver cancers, the effectiveness of intensity-modulated proton therapy (IMPT) relative to intensity-modulated photon radiotherapy (commonly referred to as IMRT). The overall long-term goal and the expected outcome ofthe proposed research is the development of proton therapy strategies which maximally exploit the physical as well as biological properties of protons to improve clinical outcomes. The common theme ofthe proposed trials is acute and late toxicity reduction, quality of life (QOL) improvement and, potentially, improvement in local control and survival. This project supports the mission ofthe NCI to improve the treatment and continuing care of cancer patients.